An increase in sensitivity to the pressor effects of tyramine, an indirectly acting sympathomimetic agent, is a well known side effect of MAO inhibitor treatment. Using an intravenous tyramine steady state infusion technique we are studying the effects of the selective inhibition of the A and B forms of MAO on tyramine's pressor effects in patients treated with clorgyline, pargyline and deprenyl. Our data suggest that treatment with clorgyline is associated with the greatest increases in tyramine sensitivity, while treatment with deprenyl or pargyline is associated with lesser increases in tyramine sensitivity. Changes in circulating norepinephrine accompanying the pressor changes induced by tyramine are being studied in unmedicated normal volunteers and in depressed patients before and after treatment with selective MAO inhibitors. Preliminary data has raised the possibility that a supersensitivity of the peripheral alpha-adrenergic receptor may contribute to the increased tyramine sensitivity observed during chronic MAO inhibition. We are also studying the effect of clinical state change in bipolar patients on tyramine response sensitivity, as well as the behavioral effects of tyramine-induced peripheral noradrenergic actvation in patients and normal volunteers.